剣持 敬

Objective. In Japan, > 80% of kidney transplantations (KTs) are performed from living donors because of a severe shortage of deceased donors. Moreover, > 90% of deceased donors are non heart-beating donors. In this study, we compared the quality of life (QOL) of the recipients between living- and deceased-donor KT performed in our hospital. Methods. QOLs of 91 recipients (11 deceased donors and 80 living donors) were analyzed using the Short Form 36 before and 1, 2, and 3 years after KT. Changes in QOLs were compared between deceased-donor KT (group DD) and living-donor KT (group LD). Results. In group DD, physical (PCS) and mental (MCS) component summary scores before transplantation were 43.7 and 48.7, respectively. PCS decreased to 35.3 at 1 year and 34.2 at 2 years, but increased to 52.6 at 3 years. MCS as 43.2 at 1 year, 52.2 at 2 years, and 44.5 at 3 years. In group LD, PCS and MCS before transplantation were 36.9 and 42.6, respectively. PCS increased to 43.3 at 1 year, 47.6 at 2 years, and 51.0 at 3 years, and MCS increased to 47.8 at 1 year, 50.1 at 2 years, and 49.6 at 3 years. Conclusions. The recipients of living-donor KT showed an improvement of QOL immediately after transplantation. However, in the recipients of deceased-donor KT, physical QOL (PCS) decreased for 2 years after transplantation. The reasons seem to be long waiting period and the use of non heart-beating donors in deceased-donor KT in Japan.

A 36-year-old woman underwent ABO-incompatible living-donor kidney transplantation. Immunosuppression was achieved by quadruple therapy with tacrolimus, basiliximab, mycophenolate mofetil (MMF), and prednisone. Desensitization and removal of anti-ABO antibody was achieved by administration of MMF for 4 weeks before transplantation followed by intravenous administration of rituximab, double-filtered plasmapheresis, and plasma exchange. At 1 month after transplantation, she complained of left ear pain without vesicle rash, tinnitus, and vertigo. Physical examination revealed left facial paralysis and nystagmus. T2 fluid-attenuated inversion recovery magnetic resonance imaging (MRI) visualized swelling of the left facial nerve. Real-time polymerase chain reaction showed the existence of varicella zoster virus DNA in the patient's tears and saliva. The final diagnosis was Ramsay Hunt syndrome without vesicle rash, which is called zoster sine herpete. The patient was treated by intravenous administration of acyclovir (3 mg/kg, 3 times per day) in addition to the reduction of the MMF dose. For facial nerve palsy, prednisolone was prescribed for 3 days and then gradually tapered. These treatments improved the symptoms of tinnitus and vertigo after a month; the facial nerve palsy completely disappeared after 10 months. This case demonstrated MRI to be a useful modality for the early diagnosis of Ramsay Hunt syndrome without vesicle eruption.

For a safe living pancreas donoration for transplantation, we evaluated the function of the residual pancreas head using 11C-methionine positron emission tomography (PET) in 13 cases before and after distal pancreatectomy. After 6 hours of fasting, we intravenously administered 11C-methionine (370 to 740 MBq), performing PET at 30 minutes thereafter. 11C-methionine PET uptake in the pancreas head was expressed as a standardized uptake value (SUV) for comparison before versus after surgery: 17.3 +/- 2.5 versus 17.4 +/- 4.9, respectively, demonstrating no significant difference. However, the changes in SUVs of the residual pancreas head showed three patterns after surgery. The SUVs were elevated in three donors after surgery, hypermetabolite type; maintained in five donors, normometabolite type; and decreased in five donors hypometabolite type. The percentages of subjects with a postoperative HbA1c value more than 5.8%, the upper normal limit, were 33% in hypermetabolite type; 40% in the normometabolite type; and 60% in the hypometabolite type. Although diabetes mellitus has not developed in any of the 13 donors, the pancreatic head function after distal pancreatectomy was slightly decreased, especially among the hypometabolite type. To avoid postoperative diabetes mellitus for a prolonged period, donors who show decreased SUVs after surgery should be strictly followed. In conclusion, 11C-methionine PET may be a potent modality to evaluate segmental pancreatic function for a safe living donor pancreatectomy.

Purpose. The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brain heart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from non heart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term. Procedures. We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CID). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 x 10(4). After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase 111 was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies. Main findings. Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD. Conclusions. Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

Background The simultaneous transplantation of pancreas and kidney from live donors is performed in select countries. One of the reasons for this reduced applicability is the invasiveness of the donor operation. We propose the method of laparoscopic-assisted operation to be performed on live donors with minimal invasion. Method The donor was placed in the right lateral decubitus position. A 7-cm upper midline incision was made, and a handport was installed in addition to two or three 12-mm ports. After the removal of the left kidney graft, the spleen and the distal part of the pancreas were completely mobilized. The splenic vein and artery were identified and mobilized. The donor was then rotated to a supine position. Dissection of the pancreatic parenchyma using ultrasound shears and ligation of the splenic vessels were performed through midline incision under direct vision. The distal part of the pancreas and the spleen were extracted. Results Since December 2007, 3 donors have undergone this operation. In all 3 cases, the postoperative course was uneventful, and both the renal and pancreatic grafts functioned well. Conclusion This technique is minimally invasive and safe, and may become the standard method of live donor operation for simultaneous pancreas-kidney transplantation.

Background/purpose Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. Methods Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. Results No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). Conclusions Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes.

The results of clinical islet transplantation in Japan are, here in, reported and discussed its efficacy and problems. Since the first islet transplantation was performed in 2004, 65 islet isolations and 34 islet transplantations to 18 type 1 diabetic patients have been performed in Japan. Following islet transplantation, patients experienced decreased insulin requirements and lower hemoglobin A1C levels, and positive serum C-peptide levels. All patients achieved stabilized blood glucose levels and the disappearance of hypoglycemic unawareness. Although three patients achieved insulin independency for a limited period, persistent islet graft function was difficult to maintain. Overall islet graft survival was 86.5% at 6 months, 78.7% at 1 year, and 62.9% at 2 years after the first islet transplantation. In our institution, we carried out 23 islet isolations and six islet transplantations to four patients. Although insulin independency was not achieved, all patients showed a disappearance of hypoglycemic unawareness. Using data from the Japanese Trial of Islet Transplantation, the effectiveness of islet transplantation was shown even when using the pancreata from non-heart-beating donors. Although there are a number of problems to be solved and further improvement is needed, we can state that the introduction of clinical islet transplantation offers hope for type 1 diabetic patients.